Back to resultsA Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease (XMaS)
Primary Purpose
Crohn Disease
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Xanthohumol
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Crohn Disease focused on measuring Crohn's Disease, Inflammatory Bowel Disease, IBD, Xanthohumol, Humulus lupulus, Hops
Eligibility Criteria
Inclusion Criteria:
- Adults 21-50 years of age
- Active Crohn's disease not in remission based on a CDAI score >150
- Willing to take isolated Xanthohumol as a dietary supplement for 8 weeks
- Willing to have blood drawn bi-weekly and fast for 10-12 hours before blood draws
- Willing and able to collect bi-weekly stool samples at home
- Willing and able to collect a 24-hour urine sample before each study visit
- Able to speak, read and understand English
- Must be able to provide written informed consent
- Non-smokers (including tobacco and Cannabis products, combusted or vaporized)
- For individuals of child-bearing potential, willingness to use an intrauterine device (IUD) or two other concurrent forms of birth control (e.g., 2 of the following categories: condoms, spermicide-containing gels, films or sponges; and/or vaginal rings) to prevent pregnancy while enrolled
Exclusion Criteria:
- Highly variable dosing of anti-inflammatory medications (dose changes more than 1x per week)
- Currently or recent (within last 14 days) taking any dietary supplements containing xanthohumol, flavonoids, or other known "anti-inflammatories" including: curcumin, turmeric, fenugreek, hops, rosemary, ginger, white willow, devil's claw, fish oil (doses>1 g/day), or quercetin. Candidates will be given the option to "wash out" for 14 days and re-contact the study team.
- Consumption of more than 1 beer per day.
- Currently receiving intravenous nutrition support therapy (or within the last 14 days)
- Currently taking anti-coagulant or anti-platelet prescription medications (or they were taken within the last 14 days)
- Currently taking antibiotic, antiparasitic, or antifungal medications orally or intravenously (or they were taken within the last 14 days)
- Initiation of or changes to supplements or medications within 14 days prior to screening.
- Initiation of or changes to an exercise regimen within 14 days prior to screening.
- Initiation of or changes to a food plan within 14 days prior to screening.
- Current involvement or within 14 days prior to screening of a significant diet or weight loss program (such as NutriSystem, Jenny Craig, Atkin's or other low-carb diet programs) or very low-calorie liquid diet programs (such as Optifast, Medifast, and/or HMR)
- Hospitalization (for any reason other than a scheduled medical procedure) within 3 months prior to screening
- Gastrointestinal surgery within 3 months prior to screening
- Malignancy within the last 5 years (with the exception of basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ of the cervix)
- Women who are lactating, pregnant or planning pregnancy within the next four months
- Typical intake of more than 2 alcohol-containing beverages per day, more than 14 per week, or more than 4 in any single day within the past 14 days.
- Smoking tobacco or nicotine products (combusted or vaporized)
- Use of illicit drugs/substances (such as but not limited to cocaine, phencyclidine (PCP), and methamphetamine) within 14 days of screening
- Use of inhaled or ingested Cannabis products, including Cannabidiol (CBD)
- Currently participating in another interventional research study, or participated in another interventional research study within 14 days of screening
- Do not have an active primary care provider or specialist (i.e., gastroenterologist) managing their CD
Sites / Locations
- National University of Natural MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Xanthohumol
Placebo
Arm Description
Participants will take capsules containing 24 mg of xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal.
Participants will receive capsules filled with a rice protein vehicle by mouth once daily with the first daily meal.
Outcomes
Primary Outcome Measures
Change from Baseline: Aspartate aminotransferase (AST)
Aspartate aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Change from Baseline:Alanine aminotransferase (ALT)
Alanine aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Change from Baseline: gamma-Glutamyl transferase (GGT)
Gamma-glutamyl transferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Change from Baseline: Estimated glomerular filtration rate
Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Change from Baseline: Blood urea nitrogen to creatinine ratio
Blood urea nitrogen:creatinine is a ratio of serum concentrations of two compounds associated with renal function. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Change from Baseline: Complete blood count
Enumeration of the various subtypes of blood cells (i.e., red blood cells, white blood cells, and platelets), plus indices including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and hemocrit. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Secondary Outcome Measures
Change from Baseline: Composite Symptoms: Crohn's Disease Activity Index (CDAI)
The Crohn's Disease Activity Index or CDAI is frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit. A CDAI score of less than 150 is considered to be remission, a score greater than 220 is considered to define moderate to severe disease, and a score greater than 300 is considered to be severe disease. Most major research studies on medications in Crohn's disease define response as a fall of the CDAI of greater than 70 points.
Change from Baseline: Change in fecal calprotectin levels
Fecal calprotectin, a protein associated with gut inflammation and irritable gut syndrome, will be measured by enzyme-linked immunosorbent assay, and expressed as mean change over time from baseline.
Change from Baseline: Change in plasma inflammatory markers (pg/mL)
Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, , and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The results will be expressed as change from baseline over time.
Full Information
NCT ID
NCT04590508
First Posted
September 28, 2020
Last Updated
July 4, 2023
Sponsor
National University of Natural Medicine
Collaborators
Oregon State University, Pacific Northwest National Laboratory
1. Study Identification
Unique Protocol Identification Number
NCT04590508
Brief Title
A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease
Acronym
XMaS
Official Title
A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
September 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National University of Natural Medicine
Collaborators
Oregon State University, Pacific Northwest National Laboratory
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
A pilot study to assess the safety and tolerability of an orally administered natural product derived from hops, called xanthohumol, in humans with Crohn's Disease, in order to identify a biological signature of xanthohumol exposure, and to characterize the role of xanthohumol metabolism by intestinal microorganisms in that signature within adults with Crohn's Disease.
Detailed Description
This is a double-masked, placebo controlled, randomized clinical trial of xanthohumol, which is a constituent of hops (Humulus lupulus). Hops and its constituents have a long history of use for a variety of conditions. However, knowledge is limited regarding the measurable biological markers of human exposure, and the role of xanthohumol metabolism by microorganisms present in the gut, particularly in individuals with gut pathologies such as Crohn's Disease. This information is necessary for the development of xanthohumol as a potential therapeutic intervention in such conditions.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn Disease
Keywords
Crohn's Disease, Inflammatory Bowel Disease, IBD, Xanthohumol, Humulus lupulus, Hops
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Participants will be randomized to receive either encapsulated xanthohumol in a rice protein vehicle, or an identical capsule containing vehicle alone.
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
Randomization will occur in up to 8 blocks of 4 based on biological sex. Initial randomization series will be generated using readily available random sequence generators designed to do so. A series of sequential envelopes will be generated, each containing the allocation for one participant. Envelopes will be opaque and signed across the seal. The randomization "code" will be kept in a sealed envelope with a signature across the label and dated the day of creation. Study product and comparator (placebo) will be compounded and placed in identical opaque capsules outside the institution.
Allocation
Randomized
Enrollment
32 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Xanthohumol
Arm Type
Experimental
Arm Description
Participants will take capsules containing 24 mg of xanthohumol in a rice protein vehicle by mouth once daily with the first daily meal.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive capsules filled with a rice protein vehicle by mouth once daily with the first daily meal.
Intervention Type
Drug
Intervention Name(s)
Xanthohumol
Intervention Description
The xanthohumol supplement will be administered in a capsule and taken orally.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
The placebo will be administered in a capsule and taken orally.
Primary Outcome Measure Information:
Title
Change from Baseline: Aspartate aminotransferase (AST)
Description
Aspartate aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline:Alanine aminotransferase (ALT)
Description
Alanine aminotransferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: gamma-Glutamyl transferase (GGT)
Description
Gamma-glutamyl transferase is an enzyme that is often measured in blood as an indication of liver toxicity. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: Estimated glomerular filtration rate
Description
Glomerular filtration rate is estimated based on blood creatinine concentration per standard nephrology practice. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: Blood urea nitrogen to creatinine ratio
Description
Blood urea nitrogen:creatinine is a ratio of serum concentrations of two compounds associated with renal function. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: Complete blood count
Description
Enumeration of the various subtypes of blood cells (i.e., red blood cells, white blood cells, and platelets), plus indices including mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV), and hemocrit. Reported as: % abnormal, % new abnormals, and mean change from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Secondary Outcome Measure Information:
Title
Change from Baseline: Composite Symptoms: Crohn's Disease Activity Index (CDAI)
Description
The Crohn's Disease Activity Index or CDAI is frequently used to assess disease severity. It gives a score ranging from 0 to over 600, based on a diary of symptoms kept by the patient for 7 days, and other measurements such as the patient's weight and haematocrit. A CDAI score of less than 150 is considered to be remission, a score greater than 220 is considered to define moderate to severe disease, and a score greater than 300 is considered to be severe disease. Most major research studies on medications in Crohn's disease define response as a fall of the CDAI of greater than 70 points.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: Change in fecal calprotectin levels
Description
Fecal calprotectin, a protein associated with gut inflammation and irritable gut syndrome, will be measured by enzyme-linked immunosorbent assay, and expressed as mean change over time from baseline.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
Title
Change from Baseline: Change in plasma inflammatory markers (pg/mL)
Description
Circulating pro-inflammatory cytokine concentrations (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, , and IL-12p70), will be measured simultaneously with a flow cytometry-based multiplex assay. The results will be expressed as change from baseline over time.
Time Frame
2 weeks, 4 weeks, 6 weeks, and 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Adults 21-50 years of age
Active Crohn's disease not in remission based on a CDAI score >150
Willing to take isolated Xanthohumol as a dietary supplement for 8 weeks
Willing to have blood drawn bi-weekly and fast for 10-12 hours before blood draws
Willing and able to collect bi-weekly stool samples at home
Willing and able to collect a 24-hour urine sample before each study visit
Able to speak, read and understand English
Must be able to provide written informed consent
Non-smokers (including tobacco and Cannabis products, combusted or vaporized)
For individuals of child-bearing potential, willingness to use an intrauterine device (IUD) or two other concurrent forms of birth control (e.g., 2 of the following categories: condoms, spermicide-containing gels, films or sponges; and/or vaginal rings) to prevent pregnancy while enrolled
Exclusion Criteria:
Highly variable dosing of anti-inflammatory medications (dose changes more than 1x per week)
Currently or recent (within last 14 days) taking any dietary supplements containing xanthohumol, flavonoids, or other known "anti-inflammatories" including: curcumin, turmeric, fenugreek, hops, rosemary, ginger, white willow, devil's claw, fish oil (doses>1 g/day), or quercetin. Candidates will be given the option to "wash out" for 14 days and re-contact the study team.
Consumption of more than 1 beer per day.
Currently receiving intravenous nutrition support therapy (or within the last 14 days)
Currently taking anti-coagulant or anti-platelet prescription medications (or they were taken within the last 14 days)
Currently taking antibiotic, antiparasitic, or antifungal medications orally or intravenously (or they were taken within the last 14 days)
Initiation of or changes to supplements or medications within 14 days prior to screening.
Initiation of or changes to an exercise regimen within 14 days prior to screening.
Initiation of or changes to a food plan within 14 days prior to screening.
Current involvement or within 14 days prior to screening of a significant diet or weight loss program (such as NutriSystem, Jenny Craig, Atkin's or other low-carb diet programs) or very low-calorie liquid diet programs (such as Optifast, Medifast, and/or HMR)
Hospitalization (for any reason other than a scheduled medical procedure) within 3 months prior to screening
Gastrointestinal surgery within 3 months prior to screening
Malignancy within the last 5 years (with the exception of basal cell carcinoma, squamous cell carcinoma, and/or carcinoma in situ of the cervix)
Women who are lactating, pregnant or planning pregnancy within the next four months
Typical intake of more than 2 alcohol-containing beverages per day, more than 14 per week, or more than 4 in any single day within the past 14 days.
Smoking tobacco or nicotine products (combusted or vaporized)
Use of illicit drugs/substances (such as but not limited to cocaine, phencyclidine (PCP), and methamphetamine) within 14 days of screening
Use of inhaled or ingested Cannabis products, including Cannabidiol (CBD)
Currently participating in another interventional research study, or participated in another interventional research study within 14 days of screening
Do not have an active primary care provider or specialist (i.e., gastroenterologist) managing their CD
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ryan Bradley, ND/MPH
Phone
503.552.1804
Email
rbradley@nunm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
John Phipps, PhD
Phone
503.552.1744
Email
jphipps@nunm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan Bradley, ND/MPH
Organizational Affiliation
National University of Natural Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
National University of Natural Medicine
City
Portland
State/Province
Oregon
ZIP/Postal Code
97201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Emily Stack
Phone
503-552-1777
Email
microbiome@nunm.edu
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We will use the University of California San Diego (UCSD) Metabolomics Workbench for sharing metabolomics datasets and results (including raw data matrices, platform information, and associated metadata).
For activity-based proteomics data, we will use PRIDE or the MassIVE data repository at UCSD.
Nucleic acid sequence data will be submitted to the National Center for Biotechnology Information (NCBI) Short Read Archive.
Gene expression data will be submitted to Gene expression Omnibus at NCBI. Microbiome metadata will be deposited into database of Genotypes and Phenotypes.
Metagenomic nucleic acid sequence data will additionally be deposited in Metagenomic Rapid Annotations using Subsystems Technology (MG-RAST) at Argonne National Laboratory, along with associated metadata.
Microbiome summary files (e.g., tables cataloging: sample metadata, taxon or protein family abundances across samples) publicly available through github.
IPD Sharing Time Frame
We will share our data no later than on acceptance of the first publication of the findings from the respective data set(s).
Citations:
PubMed Identifier
36273173
Citation
Langley BO, Ryan JJ, Phipps J, Buttolph L, Bray B, Aslan JE, Metz TO, Stevens JF, Bradley R. Xanthohumol microbiome and signature in adults with Crohn's disease (the XMaS trial): a protocol for a phase II triple-masked, placebo-controlled clinical trial. Trials. 2022 Oct 22;23(1):885. doi: 10.1186/s13063-022-06782-z.
Results Reference
derived
Learn more about this trial
A Phase 2 Clinical Trial: Xanthohumol Metabolism and Signature (XMaS) in Crohn's Disease
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